The purpose of the Animal Genomics Shared Resource (AGS) is to create (and through cryopreservation, maintain) transgenic and knockout models for human diseases including cancer. The specific objectives are: 1) Provide consultation on transgene and targeting construct design; 2) Introduce DNA into zygotes or embryonic stem cells; 3) Create founder animals or chimeras that incorporate the desired, DNA addition or change; and 4) Cryopreserve mouse embryos for cost-effective, long-term storage of genetically engineered mice. The Transgenic mouse service was created in 1989. The ability to create knockout mice was added in 1997. Cryopreservation of mouse embryos has been performed since 2000. The creation of novel mouse strains, either by transgenesis or homologous recombination, allows many members of the Yale Cancer Center (YCC), to determine the normal function of genes and how perturbation of that function can result in aberrant development or diseases such as cancer. Investigators can use AGS to create direct analogs of mutations involved in human disease, thus providing models that can be studied in a way that human subjects cannot. The ability to create such induced mutants allows investigators to effectively use mouse genetics to dissect and analyze complicated developmental pathways, biochemical processes, and biomolecular interactions in a mammal to a level previously unattainable before such technology existed. This enables researchers to investigate biological processes at a far deeper level than in vitro methods such as biochemistry or cell culture will allow, and through the appearance of novel phenotypes resulting from induced mutations, discover new relationships between these processes and pathways. Cryopreservation of mouse strains allows investigators to more efficiently utilize their financial resources in research while maintaining valuable strains for future use. The YCC AGS produces 40-60 transgenic mouse strains/year, and creates 15-20 new targeted mutant mouse models/year. Animal Genomics Services has been a shared resource of the YCC since 1989. AGS moved into new space designed specifically for their use with the completion of The Anylan Center building in 2002. Twenty-eight YCC investigators used AGS in 2005 for a total of approx. 62% of all usage of the resource. All YCC usage during 2005 was from peer-reviewed scientists from 7 of 8 YCC Research Programs